In 1959 spontaneous autoantibody production was discovered in New Zealand mice. Subsequent studies demonstrated a striking similarity of New Zealand Black mice to patients with idiopathic acquired hemolytic anemia and New Zealand Black x White F1 hybrids to humans with systemic lupus erythematosus. Numerous experiments have indicated that genetic and/or viral inter-relationships with lymphoid elements are critical for disease pathogenesis in mice. However, the precise role of the thymus and spleen and their respective subpopulations in the development of autoimmunity and lymphoproliferative disease remains unclear. It is proposed herein to create two unique animal models to resolve these issues. These models are 1) production of congenitally athymic (nude) New Zealand Black (NZB), New Zealand White (NZW) and NZB times NZW F1 mice, and 2) the production of gongenitally asplenic NZB, NZW and NZB x NZW F1 mice. The natural history and immune responsiveness of these mutant colonies will be studied and compared to littermate controls. Further, specific experiments in transplantation and cell transfer of thymus and spleen from syngeneic mice of different serial ages will be designed to identify the relationships between alterations in lymphoid subpopulations with age and development of autoimmunity and lymphoproliferative disease. BIBLIOGRAPHIC REFERENCE: Gershwin, M.E., Ikeda, R.M., and Kawakami, T.G. Immunobiology of heterotransplanted tumors in nude mice. J. Nat. Cancer Inst., (in press, May, 1977 issue).